Anticonvulsant effect of carnosine on penicillin-induced epileptiform activity in rats

Kozan, Ramazan; Sefil, Fatih; Bağirici, Faruk

doi:10.1016/j.brainres.2008.08.019

Cited by 24 publications

(14 citation statements)

References 29 publications

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“…It is reported that carnosine could readily pass through the blood brain barrier (BBB), and acts as the precursor of transmitter of histaminergic neuron system and effectively regulate brain histamine level [16], [41], [42]. The role of brain histamine in regulating stress response has recently been documented [43], [44], and the anti-stress action of exogenous histamine has been demonstrated [17].…”

Section: Discussionmentioning

confidence: 99%

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Tsoi

et al. 2012

PLoS ONE

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Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU10/spleen) while the activity of a single NK cell (LU10/106 cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.

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Section: Discussionmentioning

confidence: 99%

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Tsoi

et al. 2012

PLoS ONE

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“…Besides, it was found that carnosine could be transformed into histidine, which is important for the synthesis of histamine in the brain, and act on histaminergic neurons system to relieve stress-induced damages (48,53,54). Carnosine presumably exerted its anti-stress effect by passing through the BBB (55). On the other hand, it was found that glucocorticoid could depress the expression of histidine decarboxylase (56).…”

Section: Discussionmentioning

confidence: 99%

Carnosine Ameliorates Stress-Induced Glucose Metabolism Disorder in Restrained Mice

Tsoi

Yang

et al. 2011

J Pharmacol Sci

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Abstract. Carnosine is a natural dipeptide that has shown multiple benefits in the treatment of various diseases. This study investigated the ameliorative effects of carnosine on glucose metabolism in restraint-stressed mice. Our results showed that restraint stress could significantly influence glucose metabolism, as reflected by lowered glucose tolerance, hepatic and muscle glycogen content, and increased plasma corticosterone concentration in mice. Oral administration of carnosine (150 and 300 mg/kg) not only reverted stress-induced decline in glucose tolerance and glycogen content in liver and muscle, but also reduced plasma corticosterone level. Carnosine has also significantly suppressed mRNA expression of glucose-6-phosphatase, while elevating glycogen synthase 2, glucokinase and glucose transporter 2 expressions in the liver. The obtained results demonstrated the harmful effects induced by restraint stress, while proving that carnosine could ameliorate stress-induced glucose metabolism disturbance. It is presumable that carnosine exerts its anti-stress effects by indirectly affecting the histaminergic neuron system, modulating the stress-activated hypothalamic-pituitary-adrenal axis and improving glucose metabolism through regulation of the enzymes in the glucose metabolic pathways.

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“…Carnosine appears to possess anticonvulsant activity in rats (Wu et al, 2006;Kozan et al, 2008) and mice . It is interesting to note that treatment of humans with anticonvulsants gabapentin and topiramate raise levels of homocarnosine, a carnosine homologue, in cerebrospinal fluid (CSF) (Petroff et al, 1998 and2006), and that, while carnosine is absent from human CSF, the levels of CSF homocarnosine decrease markedly with age (Jansen et al, 2006;Huang et al, 2005).…”

Section: Carnosine Anti-convulsant Activity and Agingmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

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Carnosine ( -alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine's enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms reponsible remain uncertain. In addition to carnosine's well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nemtodes extend organism lifespan, hence carnosine's anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine's real in vivo functions. More experimentation is clearly required. ACCEPTED MANUSCRIPT 3 Carnosine and ageing.The naturally-occurring dipeptide carnosine ( -alanyl-L-histidine) has been described as forgotten and enigmatic (Bauer, 2005): the present paper is an attempt to rectify the former opinion, but, however only adds to the latter view. Amongst carnosine's enigmatic properties are its apparent anti-ageing actions; the dipeptide is one of a very few naturally-occurring compounds which suppresses cell senescence, induces rejuvenating effects Holliday, 1994 and, and protects against telomere shortening (Shao et al., 2004) in cultured human fibroblasts. The dipeptide also extends the life-span of senescence-accelerated mice (Yuneva et al., 1999) and Drosophila (Yuneva et al., 2002). There are many possible mechanisms by which carnosine exerts these anti-ageing actions however, some of which were summarized a decade ago (Hipkiss, 1998). Meanwhile there have been a number of publications suggesting further possible routes by which carnosine could suppress

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Anticonvulsant effect of carnosine on penicillin-induced epileptiform activity in rats

Cited by 24 publications

References 29 publications

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Carnosine Ameliorates Stress-Induced Glucose Metabolism Disorder in Restrained Mice

On the enigma of carnosine’s anti-ageing actions

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